Since its funded initiation in April, 1999, the Pediatric Brain Tumor Consortium (PBTC) has successfully pursued its mission to study novel therapeutic approaches for children with brain tumors. The Consortium and its member institutions propose to continue progress in its major goals: to identify new treatments for these diseases including those that are technically challenging; to ensure that laboratory discoveries relevant to children with brain cancers are rapidly translated into the clinical setting; to define the role of neuroimaging in the setting of novel approaches. Research plans are proposed in the major pediatric brain tumor types, emphasizing those tumor systems that are associated with poor outcome measured by disease control or quality of life. The PBTC is a highly interactive, multidisciplinary group dedicated to further translating the recently identified biological understandings of CNS tumors into tests of new, targeted biological therapies. The Consortium is able to pursue unique clinical trials in new cytototic and anti-angiogenic agents, in addition to local delivery trials that address intrathecal regional chemotherapy and direct neurosurgical drug administration; a study testing intra-perilesional administration of a new biological conjugate by enhanced convection delivery is convection delivery is awaiting final FDA approval. Trials include Phase I and II pharmacologic agents, alone or in combination with irradiation and studies include major research objectives related to neuroimaging, pharmacokinetic and key biological questions. The PBTC has developed an efficient, technologically sophisticated Operations and Biostatistics Center (OBC) that facilitates protocol development and regulatory review while overseeing and reporting protocol conduct within the 11-member group. The Consortium developed and secured initial funding for a Neuroimaging Center (NIC) as a resource for correlative research and will reap the fruits of these investments in the coming grant period. The Consortium is supported by a unique, completely electronic distributed database system, and the first successfully developed, systematically utilized electronic imaging submission and distribution system linking member institutions withy the Boston NIC via the OBC.